Differential expression of Lp-PLA2 in obesity and type 2 diabetes and the influence of lipids

Aims/hypothesis Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a circulatory macrophage-derived factor that increases with obesity and leads to a higher risk of cardiovascular disease (CVD). Despite this, its role in adipose tissue and the adipocyte is unknown. Therefore, the aims of this study were to clarify the expression of Lp-PLA2 in relation to different adipose tissue depots and type 2 diabetes, and ascertain whether markers of obesity and type 2 diabetes correlate with circulating Lp-PLA2. A final aim was to evaluate the effect of cholesterol on cellular Lp-PLA2 in an in vitro adipocyte model. Methods Analysis of anthropometric and biochemical variables from a cohort of lean (age 44.4 ± 6.2 years; BMI 22.15 ± 1.8 kg/m2, n = 23), overweight (age 45.4 ± 12.3 years; BMI 26.99 ± 1.5 kg/m2, n = 24), obese (age 49.0 ± 9.1 years; BMI 33.74 ± 3.3 kg/m2, n = 32) and type 2 diabetic women (age 53.0 ± 6.13 years; BMI 35.08 ± 8.6 kg/m2, n = 35), as part of an ethically approved study. Gene and protein expression of PLA2 and its isoforms were assessed in adipose tissue samples, with serum analysis undertaken to assess circulating Lp-PLA2 and its association with cardiometabolic risk markers. A human adipocyte cell model, Chub-S7, was used to address the intracellular change in Lp-PLA2 in adipocytes. Results Lp-PLA2 and calcium-independent PLA2 (iPLA2) isoforms were altered by adiposity, as shown by microarray analysis (p < 0.05). Type 2 diabetes status was also observed to significantly alter gene and protein levels of Lp-PLA2 in abdominal subcutaneous (AbdSc) (p < 0.01), but not omental, adipose tissue. Furthermore, multivariate stepwise regression analysis of circulating Lp-PLA2 and metabolic markers revealed that the greatest predictor of Lp-PLA2 in non-diabetic individuals was LDL-cholesterol (p = 0.004). Additionally, in people with type 2 diabetes, oxidised LDL (oxLDL), triacylglycerols and HDL-cholesterol appeared important predictors, accounting for 59.7% of the variance (p < 0.001). Subsequent in vitro studies determined human adipocytes to be a source of Lp-PLA2, as confirmed by mRNA expression, protein levels and immunochemistry. Further in vitro experiments revealed that treatment with LDL-cholesterol or oxLDL resulted in significant upregulation of Lp-PLA2, while inhibition of Lp-PLA2 reduced oxLDL production by 19.8% (p < 0.05). Conclusions/interpretation Our study suggests adipose tissue and adipocytes are active sources of Lp-PLA2, with differential regulation by fat depot and metabolic state. Moreover, levels of circulating Lp-PLA2 appear to be influenced by unfavourable lipid profiles in type 2 diabetes, which may occur in part through regulation of LDL-cholesterol and oxLDL metabolism in adipocytes

Retrospective analysis of coagulation parameters at epidural anaesthesia catheter withdrawal after esophageal resection

The gCube System - gCube Switch Button Widget -------------------------------------------------- gCube Switch Button Widget is a GWT Widget that can be used as a Checbox with a iOS sliding effect. This software is part of the gCube Framework (https://www.gcube-system.org/): an open-source software toolkit used for building and operating Hybrid Data Infrastructures enabling the dynamic deployment of Virtual Research Environments by favouring the realisation of reuse oriented policies. The projects leading to this software have received funding from a series of European Union programmes including: * the Sixth Framework Programme for Research and Technological Development - DILIGENT (grant no. 004260); * the Seventh Framework Programme for research, technological development and demonstration - D4Science (grant no. 212488), D4Science-II (grant no. 239019),ENVRI (grant no. 283465), EUBrazilOpenBio (grant no. 288754), iMarine (grant no. 283644); * the H2020 research and innovation programme - BlueBRIDGE (grant no. 675680), EGIEngage (grant no. 654142), ENVRIplus (grant no. 654182), Parthenos (grant no. 654119), SoBigData (grant no. 654024); Version -------------------------------------------------- 1.0.0-4.6.0-125951 (2017-07-31) Please see the file named "changelog.xml" in this directory for the release notes. Authors -------------------------------------------------- * Massimiliano Assante ([email protected]), Istituto di Scienza e Tecnologie dell'Informazione "A. Faedo" - CNR, Pisa (Italy). Maintainers ----------- * Massimiliano Assante ([email protected]), Istituto di Scienza e Tecnologie dell'Informazione "A. Faedo" - CNR, Pisa (Italy). Download information -------------------------------------------------- Source code is available from SVN: http://svn.research-infrastructures.eu/public/d4science/gcube/trunk/portlets/widgets/switch-button-widget Binaries can be downloaded from the gCube website: https://www.gcube-system.org/ Installation -------------------------------------------------- Installation documentation is available on-line in the gCube Wiki: https://wiki.gcube-system.org/gcube/index.php Documentation -------------------------------------------------- Documentation is available on-line in the gCube Wiki: https://wiki.gcube-system.org/gcube/index.php Support -------------------------------------------------- Bugs and support requests can be reported in the gCube issue tracking tool: https://support.d4science.org/projects/gcube/ Licensing -------------------------------------------------- This software is licensed under the terms you may find in the file named "LICENSE" in this directory

Fracture risk after three bariatric surgery procedures in Swedish obese subjects : up to 26 years follow-up of a controlled intervention study

Background: Previous studies have reported an increased fracture risk after bariatric surgery. Objective: To investigate the association between different bariatric surgery procedures and fracture risk. Methods: Incidence rates and hazard ratios for fracture events were analysed in the Swedish Obese Subjects study; an ongoing, nonrandomized, prospective, controlled intervention study. Hazard ratios were adjusted for risk factors for osteoporosis and year of inclusion. Information on fracture events were captured from the Swedish National Patient Register. The current analysis includes 2007 patients treated with bariatric surgery (13.3% gastric bypass, 18.7% gastric banding, and 68.0% vertical banded gastroplasty) and 2040 control patients with obesity matched on group level based on 18 variables. Median follow-up was between 15.1 and 17.9 years for the different treatment groups. Results: During follow-up, the highest incidence rate for first-time fracture was observed in the gastric bypass group (22.9 per 1000 person-years). The corresponding incidence rates were 10.4, 10.7 and 9.3 per 1000 person-years for the vertical banded gastroplasty, gastric banding and control groups, respectively. The risk of fracture was increased in the gastric bypass group compared with the control group (adjusted hazard ratio [adjHR] 2.58; 95% confidence interval [CI] 2.02–3.31; P < 0.001), the gastric banding group (adjHR 1.99; 95%CI 1.41–2.82; P < 0.001), and the vertical banded gastroplasty group (adjHR 2.15; 95% CI 1.66–2.79; P < 0.001). Conclusions: The risk of fracture is increased after gastric bypass surgery. Our findings highlight the need for long-term follow-up of bone health for patients undergoing this treatment

Risk factors of mild rectal bleeding in very low birth weight infants: a case control study

BACKGROUND: Mild rectal bleeding (MRB) is a particular clinical entity different from necrotizing enterocolitis, which significantly influences neonatal care in preterm infants. We aimed to determine the risk factors and to evaluate prospectively the clinical course of MRB. METHODS: We consecutively included in a case–control study all infants with birth weight ≤ 1500 g or gestational age ≤ 32 weeks admitted to our unit, and presenting MRB, defined as either isolated or associated with mild clinical or radiological signs. We matched each Case with two Controls. Clinical data before, after and at time of MRB were collected, together with stool cultures at time of MRB (or at similar postnatal age in Controls). Multiple logistic regression analysis was performed to determine independent risk factors for the development of MRB. RESULTS: During 4 years, among 823 very low birth weight (VLBW) infants admitted to our unit, 72 (8.8%) had MRB. The median duration of rectal bleeding was 1.1 [1–2] days and the fasting period lasted 2.9 [2–10] days. A relapse occurred in 24% of cases. In multivariate analysis, only hypertension during pregnancy (p = 0.019), growth restriction at onset of bleeding (p = 0.026), and exposure to ibuprofen (p = 0.003) were independent risk factors for MRB. In Cases there were more infants with Clostridium Difficile in stools than in Controls (p = 0.017). CONCLUSION: Hypertension during pregnancy, even without intrauterine growth restriction, appeared to carry the same risk for MRB as exposure to ibuprofen and extrauterine growth restriction